Abstract: OBJECTIVE To construct an ultra performance liquid chromatography-tandem quadru- pole mass spectrometry method to determine the concentration of losartan and its metabolite (E-3174) in rat plasma. METHODS An ACQUITY UPLC? BEH C18(100 mm×2.1 mm, 1.7 μm) column was used as the stationary phase at 30 ℃ on Waters XEVO TQD. The mobile phase was consisted of acetonitrile and water ( containing 0.01% formic acid and 0.05% ammonia water) (60∶40). The flow rate was 0.2 mL·min^-1. Plasmas were precipitated with 200 μL acetonitrile and centrifugated at 13 000 r·min^-1 for 10 min. RESULTS The retention time of E-3174 was 1.54 min. Excellent linear calibration curves of E-3174 was obtained in the concentration range of 12.5-1 600 ng·mL^-1(r=0.999 6). The lower limit of quantification of E-3174 was 0.5 ng·mL^-1 while the average recovery was 96.6%-98.37%. The retention time of losartan was 1.38 min and the linear calibration curves of losartan was obtained in the concentration range of 12.5-1600 ng·mL^-1(r=0.999 6). The average recovery was 98.4%-100.6%. The intra and inter day relative standard deviations were<5%. There were no endogenous substances existing in the incubation system which interfered with the determination of the analyses of interest. CONCLUSION The method is accurate, simple and rapid, and suitable for the determination of losartan and its metabolite (E-3174) in rat plasma.